This project proposes to apply continued progress in the genetic and in vitro laboratory definition of DLA and non-DLA systems of histocompatibility to the induction of specific allogeneic unresponsiveness in the canine species. Special attention will be given to the potential usefulness of the early recovery phase after supralethal total body irradiation as an immunologically privileged period for the induction of allograft tolerance. An attempt will be made to identify the cellular and/or humoral mechanisms implicated in the mediation of the allogeneic unresponsiveness state(s) associated with irradiation and bone marrow transplantation, with particular reference to the possible generation of suppressor T-lymphocytes in the treated recipients. Information gained in the course of these studies will be applied to the production of organ transplant tolerance across histocompatibility barriers of progressively increasing severity, first within the Cooperstown Colony, and subsequently in outbred canine populations.